Sequential activation of oncogenes and inactivation of tumor suppressor and DNA repair genes causes human cancers. The activation and inactivation of these cancer genes can be mutations or epigenetic modification such as methylation of CpG islands and chromatin modification. My researches center on integrating biological knowledge, genome sequences, and high-throughput experiments to identify genes and genetics elements that are important for the cancer development. Positional cloning and candidate cloning of cancer genes. 1) Positional cloning of a tumor suppressor gene on human chromosome 13q12 for Esophageal squamous cell cancer (ESCC), which was carried out in collaboration with Dr. Phil Taylor. We found somatic mutations of the RNF6 gene in three ESCC primary tumors. 2) Positional cloning of a tumor suppressor gene on human chromosome 13q14 for Chronic Lymphocytic Leukemia (CLL), which was done in collaboration with Drs. Lynn Goldin, Neil Caporaso, and Kenneth Buetow. We performed mutational analysis by sequencing PCR products of three candidate genes, CLLD6, CLLD7, and CLLD8. Genome-wide analysis of allelic gene expression and genomic imprinting. We used transcribed single nucleotide polymorphism (SNP) to study allelic gene expression. Affymetrix HuSNP chip was used to identify DNA genotype and to quantitatively analyze the allele-specific gene expression. We found several chromosomal regions harboring genes that show preferential expression of one allele. We will examine the allelic expression in tumors and matched normal tissues and in populations with high and low risk of cancer. The alteration in allelic expression will be analyzed for its association with other genetic changes such as gene expression, mutation, and genotype.